The present invention relates to novel benzofuran derivatives, processes for preparing the same and a pharmaceutical composition, as a therapeutic agent for diabetic complications, containing the same.
In recent years, a marked increase in the number of diabetic patients needs urgently the treatment thereof.
As therapeutic agents for diabetes, insulin and blood sugar lowering agents have so far been used widely. However, diabetes is not a mere disorder of sugar metabolism but a disease also involving a variety of complications and therefore the therapeutic effects of the above-mentioned agents alone are not enough for the treatment of diabetes.
Main complications are neuropathy, cataract, nephritis and retinopathy and in the development of these complications as abnormal metabolism of polyols is concerned (K. H. Gabbay, Adv. Metab. Disord., 2 (2), 424 (1973)). That is, in the diabetic condition, polyols such as sorbitol are accumulated in the cell to an extraordinary extent, causing osmotic pressure increase and water swelling, which lead to cellular disturbance. Therefore, the above-mentioned diseases can be prevented and cured by inhibiting the aldose reductase activity which is essential to polyol synthesis (R. G. Judzewitsch et al., New Eng. J. Med., 308, 119 to 125 (1983); J. H. Kinoshita et al., Metabolism, 28 (1), 462 to 469 (1979)). In Japanese Unexamined Patent Publication Nos. 28074/1982 and 40478/1982, there is described aldose reductase inhibiting agents used as a remedy for diabetic complications.
In the complications such as cerebral and coronary vascular disturbances, accelerated platelet aggregation due to abnormal metabolism of arachidonic acid plays an important role for the development of the complications. That is, in the diabetic condition, the accelerated production of thromboxane A.sub.2 results in the platelet aggregation to induce thrombosis, which leads to microangiopathy (Ryutaro Takahashi, Purosutaguranzin to Byotai, Gendaikagaku Zokan, P 112 to 120 (1984)). Among the complications, nephritis and retinopathy are typical microangiopathies. These complications can be prevented and treated by inhibiting the metabolism of arachidonic acid to improve the accelerated platelet aggregation in addition to inhibiting the accumulation of polyols.